It is well known that cardiovascular disease (CVD) is a leading cause of death among patients with nonalcoholic fatty liver disease (NAFLD). However, it has been long debated whether NAFLD is an independent risk factor for CVD.

For her session at the 21st Annual Harvard Nutrition and Obesity Symposium on NAFLD, Kathleen Corey, MD, MPH, MMSc, highlighted her research on the connection and drew important conclusions for future work.¹

Dr Corey is the director of the Massachusetts General Fatty Liver Program and assistant professor at Harvard Medical School in Boston.

She started her session by giving a general overview of the connection between CVD and NAFLD, as well as the potential mechanisms linking the 2 conditions.

“We can't determine if there are specific components of NAFLD, or NASH, or fibrosis that would drive CVD risk and give us some idea of the pathogenesis connecting these two conditions,” she said.

Then she delved into her research, including the preliminary results of the PROMISE trial² and the secondary results in patients with liver stenosis.³

“I think it's safe to say that we should be concerned about CVD in our patients with NAFLD, specifically those with advanced fibrosis, and we should be working to modify traditional risk factors as well as sedentary lifestyle,” Dr Corey concluded.

She also took questions from the audience, including:

You’ve made a very strong case for comorbidities in NAFLD patients dominated by cardiovascular disease. What about the notion of a multidisciplinary approach to the management of these patients—risk stratification, risk factor assessment— right out of the gate?

“Yeah, I think that's a great point. It’s something I’ve started to really think about even more, and my patients have been calculating their ASCVD risk score when they come to see me. I’m seeing patients more and more having cardiac events that, in retrospect, probably could have been prevented or at least decrease their risk. As a hepatologist, I’m certainly trying to do this more, but I also know that having our cardiology and our endocrine colleagues involved with these patients for risk reduction would be essential.”

When we think about clinical trial design moving forward, it seems that there are hepatic endpoints to be sure, and they’ve been the main focus thus far. When it comes to these important cardiovascular endpoints, which tend to be long-horizon events, can you think of other robust surrogates that we can use to think about modifying or modulating those surrogates instead of a long-drawn trial that looks for harder endpoints?

“I do think we’re probably going to be doing these longer trials in NAFLD to look for harder outcomes, and that will enable us to be able to look at the cardiovascular outcomes. We were seeing outcomes in patients at the 2-year/25-month mark, and so I think we should be able to be looking at hard outcomes there.

“I do think that looking at changes in surrogates when you treat NAFLD is helpful, and our group has shown that treating NASH does decrease LDL profiles, changing from a B phenotype to an A [phenotype] and increasing your LDL diameter and having some other positive lipid effects.

“You may be able to look at the impact … but I think that it is harder when you’re looking at [CT angiograms] to look at that over time, because that is why you can have a change in your plaque burden or high-risk plaque. It isn’t necessarily that high risk, hard outcomes that people are looking for.”

Obviously, we’re living in a very difficult time with the COVID-19 pandemic, and we do understand that COVID-19 or SARS-CoV-2 is a thrombotic disease in some of its manifestations. Have we seen here any particular risk for those patients with NAFLD or NASH in terms of either cardiac or other outcomes in those who have developed COVID-19?

“That’s a great question. You know I have seen studies looking at defining NAFLD noninvasively, looking at their outcomes, and showing that perhaps those with NAFLD have poorer outcomes overall with COVID. I don’t know that there was any assessment of whether those were driven by [MACE], but I think that’s a fantastic thought, actually, and something that we really need to be keeping an eye on.”

For more coverage of the 21st Annual Harvard Nutrition and Obesity Symposium on NAFLD, visit our Resource Center.

—Amanda Balbi

References:

1. Corey KE. CVD and NAFLD. Talk presented at: 21st Annual Harvard Nutrition and Obesity Symposium: Nonalcoholic Fatty Liver Disease (NAFLD): Mechanisms and Novel Therapeutics; June 30, 2020; Virtual. Accessed July 1, 2020.
2. Balbi A. NAFLD is associated with an increased risk of MACE. Gastroenterol Consult. Published online July 1, 2020. https://www.consultant360.com/exclusive/gastroenterology/nafld-symposium/nafld-associated-increased-risk-mace
3. Balbi A. Can the ASCVD risk score accurately predict MACE among patients with NAFLD? Gastroenterol Cons. Published online July 2, 2020. https://www.consultant360.com/exclusive/gastroenterology/nafld-symposium/can-ascvd-risk-score-accurately-predict-mace-among